Dynamic Disruptions in Nuclear Envelope Architecture and Integrity Induced by HIV-1 Vpr
Abstract
Human immunodeficiency virus–1 (HIV-1) Vpr expression halts the proliferation of human cells at or near the G2cell-cycle checkpoint. The transition from G2 to mitosis is normally controlled by changes in the state of phosphorylation and subcellular compartmentalization of key cell-cycle regulatory proteins. In studies of the intracellular trafficking of these regulators, we unexpectedly found that wild-type Vpr, but not Vpr mutants impaired for G2 arrest, induced transient, localized herniations in the nuclear envelope (NE). These herniations were associated with defects in the nuclear lamina. Intermittently, these herniations ruptured, resulting in the mixing of nuclear and cytoplasmic components. These Vpr-induced NE changes probably contribute to the observed cell-cycle arrest.
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We thank D. Morgan, T. Hunter, H. Piwnica-Worms, and H. Worman for the expression plasmids. We also thank R. Givens for administrative assistance and J. Carroll and S. Gonzalez for graphics assistance. This work was supported in part by NIH grant R01 AI145234 (to W.C.G.) and by core facilities provided by the UCSF–Gladstone Institute of Virology and Immunology, Center for AIDS Research, P30 MH59037. M.P.S. was supported by NIH/NIAID grant KO8 AI01866.
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Published In
Science
Volume 294 | Issue 5544
2 November 2001
2 November 2001
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Received: 2 July 2001
Accepted: 31 August 2001
Published in print: 2 November 2001
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- Carlos M. C. de Noronha et al.
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